We have studied tRNA binding immunoglobulins in the sera of NZB/NZW and in patients with systemic lupus erythematosus (SLE) as part of a project to obtain antibodies with conformational specificity for nucleic acids. The mice develop immunoglobulins which bind 3H-tRNA, when they develop a disease process with similarities to SLE, and we have been able to isolate these antibodies by affinity chromatography. We have also studied 3H-tRNA binding immunoglobulins by these methods in the sera of several patients with SLE. This binding is better inhibited by single stranded viral RNA than by the tRNA itself. We examined changes which occur within a group of isoacceptor E. coli tRNAs before and after bacteriophage MS2 infection. The pattern of reversed phase column chromatography is different from that of virus infected E. coli leucyl-tRNA isoacceptors. The RPC-5 pattern of the latter tRNA shows several new peaks of leucyl-tRNA. Aminoacylation and codon recognition studies suggest that these tRNAs are some modified forms of normal leucine tRNA isoacceptors. This modification may be involved in the mechanism of inhibition of host protein synthesis by the virus.